Memory/effector (CD45RBlo) CD4 T cells are controlled directly by IL-10 and cause IL-22–dependent intestinal pathology
| Autor: | Richard A. Flavell, Liming Hao, Samuel Huber, William T. O'Connor, Chozhavendan Rathinam, Susumu Nakae, Masahito Kamanaka, Yisong Y. Wan, Lauren A. Zenewicz, Yoichiro Iwakura, Nicola Gagliani |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pathology
medicine.medical_specialty Colon Regulatory T cell medicine.medical_treatment T cell Immunology chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Article Interleukin 22 Mice 03 medical and health sciences Interleukin 21 0302 clinical medicine immune system diseases hemic and lymphatic diseases medicine Animals Humans Immunology and Allergy Cytotoxic T cell IL-2 receptor 030304 developmental biology Homeodomain Proteins Mice Knockout 0303 health sciences Interleukins hemic and immune systems Colitis Inflammatory Bowel Diseases Interleukin-10 3. Good health Interleukin 10 medicine.anatomical_structure Cytokine Leukocyte Common Antigens Th17 Cells tissues Immunologic Memory 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20102149 |
| Popis: | Interleukin-10 acts directly on CD45RBlo but not CD45RBhi cells to control colitis upon transfer into Rag1-deficient recipients. The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10Rα). We found that Foxp3-depleted CD45RBlo (regulatory T cell [Treg cell]–depleted CD45RBlo) but not CD45RBhi CD4+ T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of Treg cell–depleted CD45RBlo CD4+ T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RBhi T cells. In contrast to the CD45RBhi transfer colitis model, in which IL-22 is protective, we found that T cell–derived IL-22 was pathogenic upon transfer of Treg cell–depleted CD45RBlo T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RBhi) and memory/effector (Treg cell–depleted CD45RBlo) cells and different ways that IL-22 impacts inflammatory bowel disease. |
| Databáze: | OpenAIRE |
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